title: Pharmaceutical equivalence by design for generic drugs: modified-release products.
abstract: The Office of Generic Drugs has ensured the high quality of generic products based upon two requirements: pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD). This paradigm has been used with success toward ensuring quality generic drug products that provide the same therapeutic benefit as the RLD. Drug products have increased in design complexity; as a result, approaches to ensure therapeutic equivalence must evolve to provide assurance of quality generic drug products. The Food and Drug Administration quality by design initiative (QbD) provides an enhanced evaluation approach by introducing the concept of a quality target product profile (QTPP). The QTPP introduces, within the context of the current regulatory framework, the quality concept of "pharmaceutical equivalence by design." This article illustrates through several examples how this QbD element in the evaluation of modified-release drug products enhances the current framework to ensure generic drug product equivalence. It achieves this by complementing the traditional paradigm, "equivalence by testing," where product equivalence is based upon inferences from a limited bioequivalence study, to one that also considers whether the drug product was developed to be an equivalent to the RLD, using appropriate quality surrogates that target "pharmaceutical equivalence by design."
authors.affiliation: Food and Drug Administration, Office of Generic Drugs, 7519 Standish Place, Rockville, Maryland 20855, USA. andre.raw@fda.hhs.gov
authors.forename: André Sirota
authors.initials: AS
authors.lastname: Raw
authors.forename: Robert
authors.initials: R
authors.lastname: Lionberger
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
mesh_terms: D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006801:Humans; D012015:Reference Standards; D013810:Therapeutic Equivalency; D014481:United States
chemical_list: D003692:Delayed-Action Preparations; D016568:Drugs, Generic